chr9-93645649-G-T

Variant names:

• chr9-93645649-G-T
• rs760648436
• NM_005392.4:c.320G>T
• PHF2 p.Arg107Leu

Variant summary

Our verdict is

Uncertain significance

+1 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005392.4(PHF2):​c.320G>T​(p.Arg107Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R107H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: PHF2 NM_005392.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.38
• Publications: 0 publications found

Genes affected

PHF2 (HGNC:8920): (PHD finger protein 2) This gene encodes a protein which contains a zinc finger-like PHD (plant homeodomain) finger, distinct from other classes of zinc finger motifs, and a hydrophobic and highly conserved domain. The PHD finger shows the typical Cys4-His-Cys3 arrangement. PHD finger genes are thought to belong to a diverse group of transcriptional regulators possibly affecting eukaryotic gene expression by influencing chromatin structure. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.252).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005392.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF2	NM_005392.4	MANE Select	c.320G>T	p.Arg107Leu	missense	Exon 4 of 22	NP_005383.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF2	ENST00000359246.9	TSL:1 MANE Select	c.320G>T	p.Arg107Leu	missense	Exon 4 of 22	ENSP00000352185.4	O75151
	PHF2	ENST00000851896.1		c.320G>T	p.Arg107Leu	missense	Exon 4 of 22	ENSP00000521955.1
	PHF2	ENST00000937581.1		c.320G>T	p.Arg107Leu	missense	Exon 4 of 22	ENSP00000607640.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.099
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.25
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Varity_R		0.68
gMVP		0.58
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs760648436;

hg19: chr9-96407931;

COSMIC: COSV63682994;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline